We wish to provide a central electron microscopy laboratory for the use of members of the program project. We propose to continue using the existing EM lab in the Department of Molecular Genetics and Cell Biology as the core lab for this purpose. As in the past the Core Lab will be a central facility providing training and materials for members of the Program Project. We have operated the lab effectively as a shared instrumentation facility and extending access to members of the Program Project has been a natural outgrowth of this philosophy. The laboratory currently contain a Philips EM 300 in excellent condition and is in the process of acquiring a Philips CM10 electron microscope, including a low dose kit and a Gatan cryospecimen holder for the Philips CM10. In addition, the laboratory contains other equipment normally used in an electron microscopy laboratory (described in the facilities available statement). The day-to-day operation of the lab is under the direction of our very competent departmental electron microscope technologist, Mr. Gerald Grofman. The overall administration of the lab will continue to be the responsibility of Dr. Robert Josephs. We have begun a program to use cryoelectron microscopy in the Core Lab. Appropriate computer image processing procedures have been implemented and a device for rapid freezing of specimens has been fabricated. These will be used in conjunction with the research proposed in Project I, II, and VII.